title: Acquisition of paclitaxel resistance via PI3K‑dependent epithelial‑mesenchymal transition in A2780 human ovarian cancer cells.
abstract: Epithelial ovarian cancer is a major cause of mortality among women with gynecological malignancies. Paclitaxel is commonly used for chemotherapy of ovarian cancer, yet its efficacy is limited by chemoresistance. Generally, drug resistance is associated with acquisition of the epithelial-mesenchymal transition (EMT) in cancer. The aim of the present study was to determine whether the EMT is involved in acquired resistance to paclitaxel in A2780 human ovarian cancer cells. Using the paclitaxel-resistant A2780/PTX cell line, we examined the cellular morphology, molecular changes, migration and proliferation consistent with the EMT. Furthermore, we found that inhibition of phosphatidylinositol 3-kinase (PI3K) activity reduced the proliferation and migration and restored their sensitivity to paclitaxel. Our study provides new insights into EMT-like phenotypic changes that are linked to paclitaxel resistance in A2780 cells. We believe that inhibition of the PI3K signaling pathway could provide a novel therapeutic approach to overcome chemoresistance and prevent metastasis during paclitaxel chemotherapy.
authors.affiliation: School of Pharmaceutical Sciences, Jiangnan University, Wuxi, Jiangsu, P.R. China.
authors.forename: Fangfang
authors.initials: F
authors.lastname: Du
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Wu
authors.forename: Yanjun
authors.initials: Y
authors.lastname: Liu
authors.forename: Teng
authors.initials: T
authors.lastname: Wang
authors.forename: Xiaowei
authors.initials: X
authors.lastname: Qi
authors.forename: Yong
authors.initials: Y
authors.lastname: Mao
authors.forename: Li
authors.initials: L
authors.lastname: Jiang
authors.forename: Yifei
authors.initials: Y
authors.lastname: Zhu
authors.forename: Yun
authors.initials: Y
authors.lastname: Chen
authors.forename: Ruiyu
authors.initials: R
authors.lastname: Zhu
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: Han
authors.forename: Jian
authors.initials: J
authors.lastname: Jin
authors.forename: Xin
authors.initials: X
authors.lastname: Ma
authors.forename: Dong
authors.initials: D
authors.lastname: Hua
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D002453:Cell Cycle / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D019008:Drug Resistance, Neoplasm; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects*; D005260:Female; D005455:Fluorescent Antibody Technique; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D017239:Paclitaxel / Q000494:pharmacology*; D058539:Phosphatidylinositol 3-Kinase / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured; D014945:Wound Healing / Q000187:drug effects
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D012333:RNA, Messenger; D058539:Phosphatidylinositol 3-Kinase; D017239:Paclitaxel